Periodontal diseases are referred to as those resulting in gingivitis or periodontitis together with the loss of teeth due to a bleeding, the formation of gingival crevices and the destruction of alveolar bones, etc. These periodontal diseases are progressed by a series of processes comprising colony formation by the periodontal disease-inducing bacteria, the penetration of the bacteria into the gingival tissues and the destruction of the gingival tissues. Briefly, salivary proteins in the saliva within oral cavity are first adsorbed to the surfaces of dentin and cement to form pellicle, and bacteria such as Streptococcus, Actinomyces, etc. are then grown on the surface of the pellicle to form a plaque. As time passes, such a plaque moves to the direction of the periapical root and at the same time anaerobic gram-negative bacteria such as Porphyromonas and Actinobacillus are grown by which these bacteria, bacterial components and bacterial metabolites are penetrated into gingival conjunctive tissues via gingival pocket epithelia to form gingival crevices. As a result of the metabolism by these bacteria, toxins such as hydrogen sulfide, ammonia, and amine which are toxic to the periodontal tissues are secreted and the tissues are directly destructed by the endotoxin such as lipopolysaccharide which is a constituting component of cell wall. At the same time, in vivo immune system is stimulated by the endotoxin, and then various kinds of cytokines such as activated oxygens, prostaglandins, leukotrienes, histamine, and interleukins are secreted to the exterior of cells by the various functions of humoral and cell-mediated immune systems to cause gingival inflammation. After collagen which is a substrate for the periodontal tissues is decomposed by the enzyme such as collagenase which is secreted by the bacteria and leukocytes, gums are retracted and periodontal diseases are developed, if these are allowed to lapse without any treatment.
As efforts to prevent the occurence of such periodontal diseases, antibacterial agents such as chlorohexidine gluconate, cetylpyridium chloride, sanguinarine and triclosan (e.g., 5-chloro-2-(2,4-dichlorophenyl)phenol) and anti-inflamnmatory agents such as triamcinolone acetanide have been developed as the agents which can kill the periodontal diseases-inducing bacteria within a short period of time and applied to the oral cavity products such as gargling solutions, dentifrices, and ointments. The oral cavity products developed hitherto, however, have disadvantages that they could not basically prevent the occurence of the periodontal diseases.
Therefore, various efforts to prevent the periodontal diseases have been extensively made in Korea in recent years which use medicinal herbs such as myrrh, Mori cortex, Cimicifugae rhizoma, green tea (e.g., Theae folium), Glycyrrhizae radix, Scutellariae radix, Taraxaci radix, Lonicerae flos, and a maize. However, the extracts of the medicinal herbs which can inhibit the production of prostaglandin which plays a major role in inducing the periodontal diseases or inhibit the activity of collagenase which decomposes the periodontal tissues have not yet been identified up to date. Current methodology is only possible to the extent that the plaque formation is inhibited or the occurrence of the periodontal diseases is inhibited with medicinal herbs which have anti-bacterial, anti-inflamatory, astriction, hemostatic or blood circulation promoting actions.
One of the most widely used methods until now in the treatment of the periodontal diseases is to use pharmaceutically active components which can inhibit the activity of an enzyme, collagenase which decomposes the periodontal tissues, or inhibit the production of prostaglandin which is an inducing agent for the periodontal diseases.
As an example of such method, U.S. Pat. No. 5,230,895 teaches that the periodontal diseases can be treated by inhibiting the enzyme activity of collagenase which decomposes the periodontal tissues using a system by which active components containing tetracycline are continuously delivered. European Laid-Open Publication No. 528 468 A1 suggests a method for treating the periodontal diseases which comprises preventing the periodontal diseases by inhibiting the production of prostaglandin which is an inducing agent of the periodontal diseases using a dentifrice and an oral cleansing agent comprising triclosan.
The pharmacologically active components listed above, however, have a limitation that they do not have both the actions on inhibiting the production of the periodontal disease-inducing agents and on inhibiting the activity of the periodontal tissue-decomposing enzyme in the course of treatment of the periodontal disease, but have either of the actions, and thus, cannot completely treat the periodontal diseases. In addition, there is a concern that various side effects may appear upon long term use of such agents because they are synthetic chemicals. Especially, tetracycline is usually administered in an amount of 1000 mg/day for 5 to 7 days with a dose of 250 mg (1 tablet) with 4 times. It is reported that when tetracycline is administered into a subject, the symptom of the disease is relieved to a clinically normal state, and if tetracycline is administered for a day after removing dental calculus, a considerably significant result is obtained. In view of a report on the long term administration of the agent with a low concentration, after tetracycline is administered with a daily dose of 1000 mg for 2 weeks and subsequently with a daily dose of 250 mg in once for 48 weeks, the results were obtained that gingivitis has clinically decreased, motile bacterial strains have been eliminated from the subgingival plaques and the depth of gingival crevice and the adsorption index that bacteria are adsorbed to the plaques have been decreased. However, if a low concentration of tetracycline is used for a long time, a considerable caution is requested because a drug resistance by gram-negative bacteria occurs frequently and the resistance also occurs frequently even if the administration of the antibiotic is ceased. Further, the use of the antibiotics has a limitation that it frequently induces side effects such as vomiting, a complaint for the ache of gastrointestinal tracts, diarrhea, dental coloring, etc. and thus, a pregnant woman and children should refrain the use of such agent.